Amino Acid Supplements for Protein Metabolism

Overseen By Marielle Engelen, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Texas A&M University

Must not be taking: Oral corticosteroids

Disqualifiers: Malignancy, Metabolic diseases, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different amino acid supplements affect protein metabolism in older adults. The goal is to understand how aging impacts the body's ability to process proteins, potentially addressing age-related health issues. Participants will test various combinations of amino acids, including Essential Amino Acids, Essential Amino Acids High, Essential Amino Acids + Hydroxy-methylbutyric acid (HMB), and Essential Amino Acids + Leucine, to determine the most effective combination. Healthy individuals aged 60-80 with stable weight for three months may qualify. As an unphased trial, this study offers a unique opportunity to contribute to scientific knowledge about aging and protein metabolism.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using oral corticosteroids, you must not have taken them within 4 weeks before the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that amino acid supplements, like those in this trial, are generally safe when taken in reasonable amounts. For Essential Amino Acids, studies indicate that consuming more than 100 grams per day is usually safe without major issues. However, excessive intake of any amino acid might cause side effects, though serious problems are rare.

No significant negative effects have been reported for the combination of Essential Amino Acids and Hydroxy-methylbutyric acid (HMB), but detailed safety information in humans remains limited. HMB itself is considered possibly safe when taken orally.

The combination of Essential Amino Acids and Leucine is also considered safe, although leucine might cause mild irritation if it contacts skin or eyes.

Total Amino Acids supplements have not shown serious side effects in humans. However, like other amino acid supplements, excessive intake can lead to problems.

In all cases, following the recommended amounts is important to avoid unwanted effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these amino acid supplement treatments because they specifically target protein metabolism, which is crucial for maintaining muscle mass, especially in older adults. Unlike standard protein supplements, these treatments focus on essential amino acids, which are vital for muscle repair and growth. Some variations also include hydroxy-methylbutyric acid (HMB) or leucine, enhancing muscle preservation and synthesis. These combinations might offer a more effective way to support muscle health in older adults compared to traditional protein supplements.

What evidence suggests that this trial's treatments could be effective for age-related metabolic changes?

This trial will study various amino acid supplements, including Essential Amino Acids (EAAs), EAAs combined with Hydroxy-methylbutyric acid (HMB), and EAAs with Leucine. Research has shown that EAAs can help build muscle and increase strength. Studies indicate that taking EAAs can improve muscle function and performance. Higher doses of EAAs have been linked to better overall protein levels in the body. When combined with HMB, EAAs may further boost muscle growth and prevent muscle breakdown. Adding leucine, a specific amino acid, to EAAs can enhance muscle building, which may be especially beneficial for older adults seeking to improve strength and muscle mass. Supplements that include all amino acids, like EAAs, also help maintain muscle size and strength. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 60-80 who have maintained a stable body weight and can move around independently. They must be able to lie down for up to 7 hours and follow the study's procedures. People with acute illnesses, unstable chronic conditions, current cancer, untreated metabolic diseases like liver or kidney disorders, recent fever, steroid use within the last month, or those who are pregnant cannot participate.

Inclusion Criteria

Stable body-weight (± 5%) for the past 3 months

Subject is judged to be in satisfactory health based on medical history, physical examination, and laboratory screening evaluations

I can lie on my back or slightly raised for up to 7 hours.

Exclusion Criteria

I have been diagnosed with cancer.

I do not have any severe or unstable illnesses right now.

Possible pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3 hours

1 visit (in-person)

Study Days

Participants undergo metabolic testing with stable isotopes and nutritional supplements

6 days

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Essential Amino Acids
• Essential Amino Acids High
• Essential Amino Acids + Hydroxy-methylbutyric acid (HMB)
• Essential Amino Acids + Leucine
• Placebo Water
• Total Amino Acids

Trial Overview The study tests how different combinations of amino acids affect protein metabolism in older adults. Participants will receive either Essential Amino Acids with HMB (a muscle health supplement), Essential Amino Acids with Leucine (an important nutrient for muscle), regular Essential Amino Acids, Total Amino Acids mixtures at high levels or placebo water to compare effects on aging-related changes in metabolism.

How Is the Trial Designed?

Group I: Healthy male older adults Experimental Treatment 6 Interventions

Healthy male older adults

Group II: Healthy female older adults Experimental Treatment 6 Interventions

Healthy female older adults

Essential Amino Acids is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Essential Amino Acids for:

• Nutritional deficiencies
• Malnutrition
• Wound healing

Approved in European Union as Essential Amino Acids for:

• Nutritional deficiencies
• Malnutrition
• Wound healing
• Parenteral nutrition

Approved in Canada as Essential Amino Acids for:

• Nutritional deficiencies
• Malnutrition
• Wound healing

Approved in Japan as Essential Amino Acids for:

• Nutritional deficiencies
• Malnutrition
• Wound healing

Who Is Running the Clinical Trial?

Texas A&M University

Lead Sponsor

Trials

156

Recruited

28,900+

Published Research Related to This Trial

A leucine-enriched whey protein supplement with lower calories significantly increases serum levels of total amino acids (TAA), essential amino acids (EAA), and leucine in healthy older adults compared to casein protein or higher calorie options.

The differences in amino acid absorption are influenced by the gastrointestinal behavior of the protein sources, with whey protein showing better digestion and absorption than casein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial. Luiking, YC., Abrahamse, E., Ludwig, T., et al.[2022]

In a study of 32 patients with severe COPD and sarcopenia, oral supplementation of essential amino acids (EAAs) for three months led to significant improvements in body weight (increased by 6 kg) and fat-free mass (increased by 3.6 kg), indicating enhanced nutritional status and muscle metabolism.

The EAA supplementation also resulted in improved physical activity (increased by 80%) and cognitive function (MMSE score improved from 19.1 to 20.8), suggesting that EAAs may positively impact overall health and quality of life in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia. Dal Negro, RW., Aquilani, R., Bertacco, S., et al.[2016]

In a study involving 12 older adults, an egg-based breakfast led to a greater net protein balance compared to a cereal-based breakfast, primarily by reducing protein breakdown.

Despite differences in plasma essential amino acid levels after the meals, muscle protein synthesis rates were similar between the egg and cereal breakfasts, indicating that the quality of protein influences protein turnover rather than directly enhancing muscle protein synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of meal protein determines anabolic response in older adults. Kim, IY., Shin, YA., Schutzler, SE., et al.[2023]

The combination of HMB, arginine, and glutamine is safe for use in treating muscle wasting in patients with AIDS and cancer, as shown in three double-blind studies involving a total of 109 participants.

Supplementation with these amino acids led to positive health outcomes, including improved emotional well-being and increased red blood cell counts, without any significant adverse health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. Rathmacher, JA., Nissen, S., Panton, L., et al.[2022]

In a study involving 19 young males, consuming high doses of essential amino acids (0.3 g/kg) significantly improved whole-body protein synthesis and breakdown during energy deficits compared to standard doses (0.1 g/kg), indicating better overall protein status.

Despite the enhanced protein turnover with high EAA intake, both high and standard EAA consumption resulted in similar rates of muscle protein synthesis, suggesting that there is a threshold for maximizing muscle protein synthesis even during energy deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: A randomized, crossover study. Gwin, JA., Church, DD., Hatch-McChesney, A., et al.[2021]

In a study involving 10 maintenance dialysis patients and 6 healthy individuals, it was found that dialysis patients had significantly lower total body clearance of certain essential amino acids (EAAs) like threonine, phenylalanine, valine, leucine, and isoleucine, indicating potential metabolic disorders in EAA processing.

The decreased clearance of branched-chain amino acids in dialysis patients suggests a defect in muscle metabolism, which could impact their overall amino acid utilization and nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of essential amino acids in chronic dialysis-patients. Chami, J., Reidenberg, MM., Wellner, D., et al.[2018]

A comprehensive review of clinical studies has established the first tolerable upper intake levels (ULs) for several essential and nonessential amino acids, indicating that they are generally well tolerated in healthy adults.

Specific ULs were determined for amino acids such as leucine (35 g/d for young adults), tryptophan (4.5 g/d), and arginine (30 g/d), which can guide safety standards for amino acid supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies. Elango, R.[2023]

In a comparison of essential amino acid (EAA) supplementation and keto-analogues (KA) in patients with chronic uremia, KA supplementation after EAA led to a reduction in urea levels and improved nitrogen balance across 9 studies.

Long-term KA treatment (3-9 months) in 7 patients resulted in notable improvements in renal function for some, with 5 patients remaining asymptomatic for periods of 3-8 months, suggesting potential benefits of KA in managing chronic kidney conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoacids in the treatment of uremia. Walser, M.[2013]

In a study involving 23 patients with moderate to severe COPD and 19 healthy older adults, free essential amino acid (EAA) supplements were found to stimulate whole body protein gain more effectively than complete protein supplements, with a 49% higher protein gain in COPD patients after EAA intake.

The results suggest that EAA supplements could be a beneficial strategy for preventing muscle wasting in COPD patients, similar to their effects observed in healthy older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults. Jonker, R., Deutz, NE., Erbland, ML., et al.[2019]

There has been a significant rise in the use of individual amino acids as dietary supplements, driven by their perceived health benefits and effects on physical and psychological performance.

Current reviews indicate that while there is some evidence regarding the safety of amino acids, most studies focus on animal research, and more comprehensive human safety data is needed, especially concerning the effects of excessive intake compared to dietary protein sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nature of human hazards associated with excessive intake of amino acids. Garlick, PJ.[2023]

Supplementing with a higher concentration of leucine (3.5 g) during moderate endurance exercise significantly increased muscle protein synthesis (MPS) by 33% compared to a lower concentration (1.87 g), indicating that leucine plays a crucial role in muscle recovery.

The study also found that whole-body protein breakdown and synthesis were lower after consuming the leucine-enriched supplement, suggesting improved protein metabolism during recovery, while key signaling pathways related to muscle growth were activated regardless of leucine concentration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Pasiakos, SM., McClung, HL., McClung, JP., et al.[2023]

In a study involving rats with uremia, essential amino acids (EAA) improved nutritional status and reduced blood urea nitrogen (BUN) levels compared to standard amino acids (SAA), indicating better efficacy for managing renal failure.

However, administering EAA requires a higher calorie and lower nitrogen ratio (Cal/N 600) to avoid complications, while SAA can be safely used at Cal/N 300, although it presents issues with nitrogen availability and plasma amino acid balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acid supplementation to hyperalimentation in uremic rats: effects of amount and composition of amino acids on nutrition and uremia. Kikuchi, T., Tanaka, H., Kokuba, Y., et al.[2019]

Citations

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essential amino acid supplementation on skeletal muscle and ... Stimulation of muscle protein synthesis (MPS) by EAAs can produce gains in muscle mass and quality, which translate to improvements in physical performance and ...

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Effects of essential amino acid (EAA) and glutamine ... After just a few days or weeks of administration, supplementation with EAAs and glutamine has shown significant effects in maintaining muscle size and strength.

3. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1360312/full

Stimulation of muscle protein synthesis with low-dose ... Essential amino acid (EAA)-based compositions have been shown to be effective stimulators of muscle protein synthesis, but the lower limit of effective dosage ...

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Efficacy of Protein and Essential Amino Acid Supplementation ... This review showed that protein and/or EAA supplementation might slightly improve PRO following lower limb surgery, with low certainty of the evidence.

5. nutritionandmetabolism.biomedcentral.com nutritionandmetabolism.biomedcentral.com/articles/10.1186/s12986-024-00820-0

Amino acids regulating skeletal muscle metabolism Branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating ...

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Side Effects of Amino Acid Supplements - PMC In the article is shown that enhanced intake of most amino acid supplements may not be risk-free and can cause a number of detrimental side effects.

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK209070/

Safety Concerns Regarding Supplemental Amino Acids - NCBI The extant scientific literature fails to support a safe upper limit for supplementation with any amino acid beyond that found in protein. There are several ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0022316623028535

The Nature of Human Hazards Associated with Excessive ... However, in general, there is little evidence of serious adverse effects in humans from most amino acid supplements. Nonetheless, for many amino acids, the data ...

9. tandfonline.com tandfonline.com/doi/full/10.1080/15502783.2023.2263409

Effects of essential amino acid supplementation on ... Thus, when considering the safe amounts of each EAA, these data indicate that more than 100 g of supplemental EAAs can be safely consumed per day in an American ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0022316622024221

International Regulations on Amino Acid Use in Foods and ... In this brief review we argue that controlling the standards of purity and ingredient quality are the key safety issues that should be considered during risk ...